Marrow transplantation for pancytopenia in dyskeratosis congenita

Mahmoud, Hossam K.; Schaefer, U. W.; Schmidt, C. G.; Becher, R.; Götz, G. F.; Richter, Hans

doi:10.1007/bf00320601

Cited by 20 publications

(10 citation statements)

References 5 publications

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“…In addition, irradiation may cause late vascular complications after bone marrow transplantation for dyskeratosis 7 and we suggest that the good results obtained by our team is due to avoidance of TBI in conditioning. [6][7][8][9][10] In our patients reduced dose of busulfan was well tolerated with no major side-effects. Also, differentiation of skin and GI lesions of this disease from chronic GVHD is not possible.…”

Section: Discussionsupporting

confidence: 51%

“…Results of allogeneic bone marrow transplantation in these patients have been relatively poor due to early and late complications. [6][7][8][9][10] We describe the effect of bone marrow transplantation for aplastic anemia in two siblings with dyskeratosis congenita from a single donor. The other brother of these two siblings had died due to bone marrow failure and dyskeratosis congenita previously.…”

Section: Discussionmentioning

confidence: 99%

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Correction of bone marrow failure in dyskeratosis congenita by bone marrow transplantation

Ghavamzadeh

Alimoghadam

Nasseri

et al. 1999

Bone Marrow Transplant

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Summary:Dyskeratosis congenita is recognized by its dermal lesions and constitutional aplastic anemia in some cases. We report successful allogeneic bone marrow transplantation in two siblings with this disease from their sister, and their long term follow-up. We used reduced doses of cyclophosphamide and busulfan for conditioning instead of total body irradiation. Also, we report late adverse effects of transplantation which are not distinguishable from the natural course of disease. Keywords: allogeneic bone marrow transplantation; constitutional anemia; dyskeratosis congenita Dyskeratosis congenita is a rare congenital syndrome characterized by atrophy and reticular pigmentation of skin, dystrophy of nails, 1 leukoplakia together with multi-system ectodermal and some mesodermal changes. Skin changes are typically located on the upper torso, neck and face, although the extremities may also be involved. Other manifestations of dyskeratosis congenita may be some other epithelial changes such as gingival disorders, dysphagia due to esophageal strictures, skeletal abnormality, aplastic anemia, 2 mental deficiency and hypersplenism.Severe aplastic anemia appears between the ages of 5 and 10 years. 3 Most of the cases transmit as an X-linked recessive inheritance pattern, although autosomal recessive 4 and autosomal dominant transmission 5 have also been reported. Results of allogeneic bone marrow transplantation in these patients have been relatively poor due to early and late complications. [6][7][8][9][10] We describe the effect of bone marrow transplantation for aplastic anemia in two siblings with dyskeratosis congenita from a single donor. The other brother of these two siblings had died due to bone marrow failure and dyskeratosis congenita previously. The parents of patients were not first cousins and were phenotypically normal.Correspondence: Dr K Alimoghadam, Shariati Hospital, Karger Aven, Tehran 14114 Iran Received 3 August 1998; accepted 8 September 1998Case report Case 1Patient 1 was an 18-year-old man with dyskeratosis congenita with reticular pigmentation, nail dystrophy, leukoplakia and marrow failure. He had received oxymetholone before BMT, with a history of frequent blood and platelet transfusion. Pulmonary function tests before bone marrow transplantation were normal. His bone marrow was hypoplastic and peripheral blood indices showed pancytopenia (Table 1).His conditioning regimen was cyclophosphamide 20 mg/kg/day for 4 days and busulfan 0.2 mg/kg/day for 4 days. Transplantation was carried out with infusion of 4.6 × 10 8 mononuclear cells per kilogram of body weight from bone marrow of his HLA-identical healthy sister. We used methotrexate and cyclosporin for GVHD prophylaxis and mild skin and gastrointestinal acute GVHD occurred after transplantation. He was discharged from hospital 37 days after marrow transplantation. On further follow-up, only his skin showed erythematous lesions and desquamation of his face, which was not possible to differentiate between chronic GVHD and dyskeratosis. He ...

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Correction of bone marrow failure in dyskeratosis congenita by bone marrow transplantation

Ghavamzadeh

Alimoghadam

Nasseri

et al. 1999

Bone Marrow Transplant

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“…Previously, results of HSCT using a myeloablative regimen for patients with DC were disappointing mainly because of pulmonary/liver complications and GVHD (12)(13)(14)(15)(16)(17)(18)(19). Until recently, there were no survivors who received unrelated sources of stem cells (3).…”

Section: Discussionmentioning

confidence: 99%

Reduced‐intensity conditioning for alternative donor hematopoietic stem cell transplantation in patients with dyskeratosis congenita

Nishio

Takahashi

Ohashi

et al. 2010

Pediatric Transplantation

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DC is an inherited bone marrow failure syndrome mainly characterized by nail dystrophy, abnormal skin pigmentation, and oral leukoplakia. Bone marrow failure is the most common cause of death in patients with DC. Because previous results of HSCT with a myeloablative regimen were disappointing, we used a reduced-intensity conditioning regimen for two patients with classic DC, and one patient with cryptic DC who harbored the TERT mutation. Graft sources included two mismatched-related bone marrow (BM) donors and one unrelated BM donor. Successful engraftment was achieved with few regimen-related toxicities in all patients. They were alive 10, 66, and 72 months after transplantation, respectively. Long-term follow-up is crucial to determine the late effects of our conditioning regimen.

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“…Presently, the only curative treatment for severe bone marrow failure is allogeneic hemopoietic stem cell transplantation. Twenty-one myeloablative procedures have been reported in the literature (27)(28)(29)(30)(31)(32)(33)(34)(35)(36), with disappointing results because of pulmonary/endothelial complications ( Table 2). None of the three patients receiving a myeloablative transplant with an unrelated source of stem cells have survived.…”

Section: Treatment Of DCmentioning

confidence: 99%

Dyskeratosis congenita: Advances in the understanding of the telomerase defect and the role of stem cell transplantation

Fuente

Dokal

2007

Pediatric Transplantation

109

111

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DC is a multisystem bone marrow failure syndrome exhibiting marked clinical and genetic heterogeneity. X-linked, autosomal dominant and autosomal recessive subtypes are recognized. The gene mutated in X-linked DC (DKC1) encodes a highly conserved nucleolar protein called dyskerin. Dyskerin associates with the H/ACA motif class of small nucleolar RNAs in small nucleolar ribonucleoprotein particles that are important in guiding the conversion of uracil to pseudouracil during the maturation of ribosomal RNA. Dyskerin also associates with the TERC, which is important in the maintenance of telomeres. Mutations in TERC have been identified in patients with autosomal dominant DC and in a subset of patients with aplastic anemia and myelodysplasia. Recently, heterozygous mutations in TERT have been found in some patients with autosomal dominant DC and aplastic anemia. Additionally, patients with the severe multisystem disorder, Hoyeraal-Hreidarsson syndrome, have been found to have DKC1 mutations. Collectively, these observations have demonstrated that classical DC, Hoyeraal-Hreidarsson syndrome and a subset of aplastic anemia are due to a primary defect in telomerase. The critical role of telomeres and telomerase in humans is seen in the multisystem abnormalities found in these patients, including the increased incidence of malignancy. As bone marrow failure is the principal cause of death, conventional allografts have been attempted with limited success due to the high rate of pulmonary and endothelial complications. However, outcomes have improved with the use of non-myeloablative protocols, although the follow up is too short to evaluate long term toxicity and the natural course of the disease and it may be that correction of the telomerase defect is essential for the treatment of these patients.

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Marrow transplantation for pancytopenia in dyskeratosis congenita

Cited by 20 publications

References 5 publications

Correction of bone marrow failure in dyskeratosis congenita by bone marrow transplantation

Correction of bone marrow failure in dyskeratosis congenita by bone marrow transplantation

Reduced‐intensity conditioning for alternative donor hematopoietic stem cell transplantation in patients with dyskeratosis congenita

Dyskeratosis congenita: Advances in the understanding of the telomerase defect and the role of stem cell transplantation

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